Background Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. Objectives Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. Data sources Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). Review methods Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000–30,000. Results A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [–20.23 kg, 95% confidence interval (CI) –23.75 to –16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of –4.41 kg (95% CI –5.93 to –2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. Limitations Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. Conclusions Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. Future work Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. Study registration This study is registered as PROSPERO CRD42016040190. Funding The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

BackgroundThe initial response to COVID-19 in the UK involved a rapid contraction of face-to-face sexual and reproductive health (SRH) services and widespread use of remote workarounds. This study sought to illuminate young people’s experiences of accessing and using condoms and contraception in the early months of the pandemic.MethodsWe analysed data, including open-text responses, from an online survey conducted in June–July 2020 with a convenience sample of 2005 16–24-year-olds living in Scotland.ResultsAmong those who used condoms and contraception, one quarter reported that COVID-19 mitigation measures had made a difference to their access or use. Open-text responses revealed a landscape of disrupted prevention, including changes to sexual risk-taking and preventive practices, unwanted contraceptive pathways, unmet need for sexually transmitted infection (STI) testing, and switches from freely provided to commercially sold condoms and contraception. Pandemic-related barriers to accessing free condoms and contraception included: (1) uncertainty about the legitimacy of accessing SRH care and self-censorship of need; (2) confusion about differences between SRH care and advice received from healthcare professionals during the pandemic compared with routine practice; and (3) exacerbation of existing access barriers, alongside reduced social support and resources to navigate SRH care.ConclusionsEmerging barriers to STI and pregnancy prevention within the context of COVID-19 have the potential to undermine positive SRH practices, and widen inequalities, among young people. As SRH services are restored amid evolving pandemic restrictions, messaging to support navigation of condom and contraception services should be co-created with young people.

Objectives To compare the effectiveness and safety of surgical interventions for women with stress urinary incontinence. Design Systematic review and network meta-analysis. Eligibility criteria for selecting studies Randomised controlled trials evaluating surgical interventions for the treatment of stress urinary incontinence in women. Methods Identification of relevant randomised controlled trials from Cochrane reviews and the Cochrane Incontinence Specialised Register (searched May 2017), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Medline In-Process, Medline Epub Ahead of Print, CINAHL, ClinicalTrials.gov, and WHO ICTRP. The reference lists of relevant articles were also searched. Primary outcomes were “cure” and “improvement” at 12 months, analysed by means of network meta-analyses, with results presented as the surface under the cumulative ranking curve (SUCRA). Adverse events were analysed using pairwise meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool. The quality of evidence for network meta-analysis was assessed using the GRADE approach. Results 175 randomised controlled trials assessing a total of 21 598 women were included. Most studies had high or unclear risk across all risk of bias domains. Network meta-analyses were based on data from 105 trials that reported cure and 120 trials that reported improvement of incontinence symptoms. Results showed that the interventions with highest cure rates were traditional sling, retropubic midurethral sling (MUS), open colposuspension, and transobturator MUS, with rankings of 89.4%, 89.1%, 76.7%, and 64.1%, respectively. Compared with retropubic MUS, the odds ratio of cure for traditional sling was 1.06 (95% credible interval 0.62 to 1.85), for open colposuspension was 0.85 (0.54 to 1.33), and for transobtrurator MUS was 0.74 (0.59 to 0.92). Women were also more likely to experience an improvement in their incontinence symptoms after receiving retropubic MUS or transobturator MUS compared with other surgical procedures. In particular, compared with retropubic MUS, the odds ratio of improvement for transobturator MUS was 0.76 (95% credible interval 0.59 to 0.98), for traditional sling was 0.69 (0.39 to 1.26), and for open colposuspension was 0.65 (0.41 to 1.02). Quality of evidence was moderate for retropubic MUS versus transobturator MUS and low or very low for retropubic MUS versus the other two interventions. Data on adverse events were available mainly for mesh procedures, indicating a higher rate of repeat surgery and groin pain but a lower rate of suprapubic pain, vascular complications, bladder or urethral perforation, and voiding difficulties after transobturator MUS compared with retropubic MUS. Data on adverse events for non-MUS procedures were sparse and showed wide confidence intervals. Long term data were limited. Conclusions Retropubic MUS, transobturator MUS, traditional sling, and open colposuspension are more effective than other procedures for stress urinary incontinence in the short to medium term. Data on long term effectiveness and adverse events are, however, limited, especially around the comparative adverse events profiles of MUS and non-MUS procedures. A better understanding of complications after surgery for stress urinary incontinence is imperative. Systematic review registration PROSPERO CRD42016049339.

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The nine Bradford Hill (BH) viewpoints (sometimes referred to as criteria) are commonly used to assess causality within epidemiology. However, causal thinking has since developed, with three of the most prominent approaches implicitly or explicitly building on the potential outcomes framework: directed acyclic graphs (DAGs), sufficient-component cause models (SCC models, also referred to as ‘causal pies’) and the grading of recommendations, assessment, development and evaluation (GRADE) methodology. This paper explores how these approaches relate to BH’s viewpoints and considers implications for improving causal assessment. We mapped the three approaches above against each BH viewpoint. We found overlap across the approaches and BH viewpoints, underscoring BH viewpoints’ enduring importance. Mapping the approaches helped elucidate the theoretical underpinning of each viewpoint and articulate the conditions when the viewpoint would be relevant. Our comparisons identified commonality on four viewpoints: strength of association (including analysis of plausible confounding); temporality; plausibility (encoded by DAGs or SCC models to articulate mediation and interaction, respectively); and experiments (including implications of study design on exchangeability). Consistency may be more usefully operationalised by considering an effect size’s transportability to a different population or unexplained inconsistency in effect sizes (statistical heterogeneity). Because specificity rarely occurs, falsification exposures or outcomes (i.e., negative controls) may be more useful. The presence of a dose-response relationship may be less than widely perceived as it can easily arise from confounding. We found limited utility for coherence and analogy. This study highlights a need for greater clarity on BH viewpoints to improve causal assessment.

BackgroundUrinary incontinence in women is a distressing condition that restricts quality of life and results in a large economic burden to both the NHS and women themselves.ObjectiveTo evaluate the clinical effectiveness, safety and cost-effectiveness of surgical treatment for stress urinary incontinence (SUI) in women and explore women’s preferences.DesignAn evidence synthesis, a discrete choice experiment (DCE) and an economic decision model, with a value-of-information (VOI) analysis. Nine surgical interventions were compared. Previous Cochrane reviews for each were identified and updated to include additional studies. Systematic review methods were applied. The outcomes of interest were ‘cure’ and ‘improvement’. Both a pairwise and a network meta-analysis (NMA) were conducted for all available surgical comparisons. A DCE was undertaken to assess the preferences of women for treatment outcomes. An economic model assessed the cost-effectiveness of alternative surgeries and a VOI analysis was undertaken.ResultsData from 175 studies were included in the effectiveness review. The majority of included studies were rated as being at high or unclear risk of bias across all risk-of-bias domains. The NMA, which included 120 studies that reported data on ‘cure’ or ‘improvement’, showed that retropubic mid-urethral sling (MUS), transobturator MUS, traditional sling and open colposuspension were more effective than other surgical procedures for both primary outcomes. The results for other interventions were variable. In general, rate of tape and mesh exposure was higher after transobturator MUS than after retropubic MUS or single-incision sling, whereas the rate of tape or mesh erosion/extrusion was similar between transobturator MUS and retropubic MUS. The results of the DCE, in which 789 women completed an anonymous online questionnaire, indicate that women tend to prefer surgical treatments associated with no pain or mild chronic pain and shorter length of hospital stay as well as those treatments that have a smaller risk for urinary symptoms to reoccur after surgery. The cost-effectiveness results suggest that, over a lifetime, retropubic MUS is, on average, the least costly and most effective surgery. However, the high level of uncertainty makes robust estimates difficult to ascertain. The VOI analysis highlighted that further research around the incidence rates of complications would be of most value.LimitationsOverall, the quality of the clinical evidence was low, with limited data available for the assessment of complications. Furthermore, there is a lack of robust evidence and significant uncertainty around some parameters in the economic modelling.ConclusionsTo our knowledge, this is the most comprehensive assessment of published evidence for the treatment of SUI. There is some evidence that retropubic MUS, transobturator MUS and traditional sling are effective in the short to medium term and that retropubic MUS is cost-effective in the medium to long term. The VOI analysis highlights the value of further research to reduce the uncertainty around the incidence rates of complications. There is a need to obtain robust clinical data in future work, particularly around long-term complication rates.Study registrationThis study is registered as PROSPERO CRD42016049339.FundingThe National Institute for Health Research Health Technology Assessment programme.

BackgroundChronic kidney disease (CKD) is a long-term condition requiring treatment such as conservative management, kidney transplantation or dialysis. To optimise the volume of fluid removed during dialysis (to avoid underhydration or overhydration), people are assigned a ‘target weight’, which is commonly assessed using clinical methods, such as weight gain between dialysis sessions, pre- and post-dialysis blood pressure and patient-reported symptoms. However, these methods are not precise, and measurement devices based on bioimpedance technology are increasingly used in dialysis centres. Current evidence on the role of bioimpedance devices for fluid management in people with CKD receiving dialysis is limited.ObjectivesTo evaluate the clinical effectiveness and cost-effectiveness of multiple-frequency bioimpedance devices versus standard clinical assessment for fluid management in people with CKD receiving dialysis.Data sourcesWe searched major electronic databases [e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index and Cochrane Central Register of Controlled Trials (CENTRAL)] conference abstracts and ongoing studies. There were no date restrictions. Searches were undertaken between June and October 2016.Review methodsEvidence was considered from randomised controlled trials (RCTs) comparing fluid management by multiple-frequency bioimpedance devices and standard clinical assessment in people receiving dialysis, and non-randomised studies evaluating the use of the devices for fluid management in people receiving dialysis. One reviewer extracted data and assessed the risk of bias of included studies. A second reviewer cross-checked the extracted data. Standard meta-analyses techniques were used to combine results from included studies. A Markov model was developed to assess the cost-effectiveness of the interventions.ResultsFive RCTs (with 904 adult participants) and eight non-randomised studies (with 4915 adult participants) assessing the use of the Body Composition Monitor [(BCM) Fresenius Medical Care, Bad Homburg vor der Höhe, Germany] were included. Both absolute overhydration and relative overhydration were significantly lower in patients evaluated using BCM measurements than for those evaluated using standard clinical methods [weighted mean difference –0.44, 95% confidence interval (CI) –0.72 to –0.15,p = 0.003,I2 = 49%; and weighted mean difference –1.84, 95% CI –3.65 to –0.03;p = 0.05,I2 = 52%, respectively]. Pooled effects of bioimpedance monitoring on systolic blood pressure (SBP) (mean difference –2.46 mmHg, 95% CI –5.07 to 0.15 mmHg;p = 0.06,I2 = 0%), arterial stiffness (mean difference –1.18, 95% CI –3.14 to 0.78;p = 0.24,I2 = 92%) and mortality (hazard ratio = 0.689, 95% CI 0.23 to 2.08;p = 0.51) were not statistically significant. The economic evaluation showed that, when dialysis costs were included in the model, the probability of bioimpedance monitoring being cost-effective ranged from 13% to 26% at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. With dialysis costs excluded, the corresponding probabilities of cost-effectiveness ranged from 61% to 67%.LimitationsLack of evidence on clinically relevant outcomes, children receiving dialysis, and any multifrequency bioimpedance devices, other than the BCM.ConclusionsBCM used in addition to clinical assessment may lower overhydration and potentially improve intermediate outcomes, such as SBP, but effects on mortality have not been demonstrated. If dialysis costs are not considered, the incremental cost-effectiveness ratio falls below £20,000, with modest effects on mortality and/or hospitalisation rates. The current findings are not generalisable to paediatric populations nor across other multifrequency bioimpedance devices.Future workServices that routinely use the BCM should report clinically relevant intermediate and long-term outcomes before and after introduction of the device to extend the current evidence base.Study registrationThis study is registered as PROSPERO CRD42016041785.FundingThe National Institute for Health Research Health Technology Assessment programme.

In fields (such as population health) where randomised trials are often lacking, systematic reviews (SRs) can harness diversity in study design, settings and populations to assess the evidence for a putative causal relationship. SRs may incorporate causal assessment approaches (CAAs), sometimes called 'causal reviews', but there is currently no consensus on how these should be conducted. We conducted a methodological review of self-identifying 'causal reviews' within the field of population health to establish: (1) which CAAs are used; (2) differences in how CAAs are implemented; (3) how methods were modified to incorporate causal assessment in SRs. Three databases were searched and two independent reviewers selected reviews for inclusion. Data were extracted using a standardised form and summarised using tabulation and narratively. Fifty-three reviews incorporated CAAs: 46/53 applied Bradford Hill (BH) viewpoints/criteria, with the remainder taking alternative approaches: Medical Research Council guidance on natural experiments (2/53, 3.8%); realist reviews (2/53, 3.8%); horizontal SRs (1/53, 1.9%); 'sign test' of causal mechanisms (1/53, 1.9%); and a causal cascade model (1/53, 1.9%). Though most SRs incorporated BH, there was variation in application and transparency. There was considerable overlap across the CAAs, with a tradeoff between breadth (BH viewpoints considered a greater range of causal characteristics) and depth (many alternative CAAs focused on one viewpoint). Improved transparency in the implementation of CAA in SRs in needed to ensure their validity and allow robust assessments of causality within evidence synthesis.